by Kathleen O’Neil
Patients with advanced cancer that has spread often do not have many treatment options, but City of Hope researchers and their colleagues may have found a way to treat such cancers more effectively.
Investigators at City of Hope and St. Jude Children’s Research Hospital used modified neural stem cells to activate and concentrate chemotherapeutic drugs predominately at tumor sites, so that normal tissues surrounding the tumor and throughout the body remain relatively unharmed.
The technique could help increase the chemotherapy doses that patients can safely tolerate, potentially increasing their cell-killing power.
“This approach could significantly improve future treatment options for patients with metastatic cancer,” said Karen Aboody, M.D., assistant professor in the divisions of Hematology & Hematopoietic Cell Transplantation and Neurosciences at City of Hope. “It not only has the potential to destroy residual tumor cells, but it should also improve patients’ quality of life by minimizing toxic side effects such as nausea, diarrhea or bone marrow suppression.”
Aboody was lead author of the study done in collaboration with senior author Mary Danks, Ph.D., associate member in the Department of Molecular Pharmacology at St. Jude Children’s Research Hospital in Memphis, Tenn. The study was published Dec. 20 in PLoS ONE; a second, related paper appears in Cancer Research this month.
Most chemotherapy drugs damage fast-growing cells in the body — whether cells are normal or cancerous — which is why the drugs are toxic to tissues such as the intestinal lining and hair follicles.
Aboody and her colleagues have developed a two-part system that may reduce that toxicity: It first infiltrates tumors, and then activates a chemotherapeutic drug, thereby providing a killing effect at the tumor site — or sites, if the tumor has spread.
The technique takes advantage of the tendency for invasive tumors to attract neural stem cells.
In their study, the researchers injected modified neural stem/progenitor cells into immunosup-pressed mice that had neuroblastoma tumors. After waiting a few days to allow the stem cells to migrate to the tumors, researchers administered a compound that is a precursor to a chemotherapeutic drug. The precursor interacts with an enzyme produced by the neural stem/progenitor cells and converts into an active drug that kills surrounding tumor cells.
The precursor drugs were administered for two weeks. Then, after a two-week break, researchers administered a second round of stem/progenitor cells and drugs.
All of the neuroblastoma mice appeared healthy and tumor-free at six months. All of the untreated neuroblastoma mice died within two-and-a-half months.
The results hold promise for treating solid tumors that metastasize, including neuroblastoma, which represents 6 to 10 percent of all childhood cancers worldwide, with higher proportions in children under age 2.
“The results are especially important in the case of high-risk neuroblastoma, because treatment-resistant cancer returns in as many as 80 percent of children, and the majority die of their disease,” Danks said.
Aboody and her colleagues had previously demonstrated the technique’s efficacy in primary and metastatic tumors in the brain. This is the first research to demonstrate that it also is effective in a metastatic cancer model, targeting many solid tumor sites spread throughout the body.
They believe that the technique could also be applied to other malignant solid tumors, including colon, brain, prostate and breast cancers, and are planning preclinical trials using those tumors.
The research was funded by grants from the National Cancer Institute, the Stop Cancer Foundation, Phi Beta Psi Sorority, the Rosalinde and Arthur Gilbert Foundation, the Neidorf Family Foundation, the Marcus Foundation and ALSAC (American Lebanese Syrian Associated Charities).